Caerulomycin A—An Antifungal Compound Isolated from Marine Actinomycetes

Abstract

Actinomycetes have been prolific sources of novel secondary metabolites with a range of biological activities that may ultimately find application as therapeutic compounds. Hence several drug discovery companies are engaged in isolation of novel bioactive metabolites from these microbial sources. Antibiotics form the major class of such bioactive metabolites and have been widely used for treating infectious diseases. One of the most critical problems in clinical practice is the increase of prevalence of drug resistant strains, especially azole resistance among fungi. Due to this, there is a constant need for development of new antifungal antibiotics having novel scaffolds and/or mechanism of action. In our in-house screening program in the quest of novel and superior antifungal compounds, an actinomycetes strain PM0525875 was isolated from a marine invertebrate. The extracts of this microbe showed potent in-vitro antifungal activity against drug resistant fungal strains. The antifungal active peak from the extract obtained by shake flask fermentation was identified by chromatographic and other analytical techniques during bioactivity guided isolation. Later the fermentation conditions were optimized in 30 L fermentor for the production of sufficient amount antifungal compound for complete structural characterization. Consequently the fermented broth extract was subjected to bioactivity-guided fractionation, to isolate the active principle using different preparative chromatographic techniques followed by its characterization. The active principle was characterized to be Caerulomycin A. Minimum inhibitory concentration (MIC) of the compound was found in the range of 0.39 -1.56 µg/ml against pathogenic fungal test strains. The phylogenetic analysis of producer strain using 16S rRNA sequence showed closest match with Actinoalloateichus cyanogriseus. Herewith we report the isolation of Caerulomycin A from marine invertebrate-associated Actinoalloteichus sp. using optimized medium and fermentation conditions.

Isolation and Characterization of Antibacterial Metabolites Produced by Streptomyces species from Escravos River, Delta State, Nigeria

“…It was also higher than the MIC values obtained by Singh et al [16] which stretched from 0.5 µg/mL to 3 µg/mL. Ambavane et al [4] also reported less MIC values ranging from 0.39 µg/mL to 1.56 µg/mL. AZ-NIOFD1 recovered from the Nile River, Egypt [52] had MIC range from 0.0117 mg/mL to 0.03125 mg/mL.…”

Current Status and Future Prospects of Marine Natural Products (MNPs) as Antimicrobials

“…The MICs of Caerulomycin A was in the range of 0.39–1.26 µg/mL. Furthermore, the MIC values obtained for Caerulomycin A against fluconazole resistant C. glabrata were comparable with the MIC values obtained for Amphotericin B [ 87 ]. Pyridones, trichodin A ( 157 ) and pyridoxatin ( 158 ), were extracted from both the mycelia and the culture broth of the marine fungus, Trichoderma sp.…”

Hypersaline Actinomycetes and Their Biological Applications

“…The number of antifungal agents available for controlling fungal infections is still limited in comparison to antibacterial agents, and their use is still risky owing to toxicity and side effects [28]. Therefore, studies are still being conducted to isolate and identify novel antifungals that are potentially effective against pathogenic fungi [23].…”